Impact of the ALLHAT Study Results on Managed Care

■■ A Closer Look at Pharmacy Technicians An important component of discussions around the pharmacy workforce shortage issue is the appropriate use of technicians in various practice settings, the extent to which technicians are licensed and regulated, and the level of training necessary for technicians. Simultaneously, the growth of the number of pharmacy technicians presents a boon to the profession and a substantive challenge. On one hand, the use of technicians helps to address the dramatic shortage of pharmacists that exists in today’s marketplace. That shortage is expected to increase. Technicians are being used in a variety of ways in many different venues. As referenced in the “2002 White Paper on Pharmacy Technicians: Needed Changes Can No Longer Wait,” it is noted that there are as many as 250,000 technicians operating in the United States. Functioning under the management of licensed pharmacists, technicians can perform repetitive, rote tasks that free pharmacists to deal with issues that necessitate their extensive training and expertise. In this manner, they provide a definite boon to the profession. On the other hand, the lack of standardization in the preparation requirements for technicians is an Achilles’ heel for the profession. While the profession vests technicians with the provision of direct service to the public, training and education requirements vary dramatically from state to state. In some jurisdictions, technicians must have successfully completed comprehensive education programs. Others mandate that technicians become certified through the Pharmacy Technician Certification Board. Employers often mandate in-service training to introduce the new technician to their roles, but this is at the discretion of the employer, creating great variations. Alarmingly, in some states, all that is required is a modest registration fee, without attestation to training of any sort. The 2002 white paper is an update of a white paper on pharmacy technicians that was originally published by the American Pharmaceutical Association and the American Society of HealthSystem Pharmacists in 1996. The Council on Credentialing in Pharmacy authorized an update to the piece to reflect the dynamic changes that have occurred in the intervening years. The Council on Credentialing in Pharmacy is dedicated to credentialing programs in pharmacy that meet established standards of quality that will contribute to significant improvement in the pharmaceutical care of patients and the overall public health. The council strives to introduce standardization into postlicensure training for pharmacists and training for technicians. Its members include: • Academy of Managed Care Pharmacy • American College of Apothecaries • American Council on Pharmaceutical Education • American Society of Consultant Pharmacists • Board of Pharmaceutical Specialties • Pharmacy Technician Certification Board • American Association of Colleges of Pharmacy • American College of Clinical Pharmacy • American Pharmaceutical Association • American Society of Health-System Pharmacists • Commission for Certification in Geriatric Pharmacy Similar to the individual pharmacist-supervisor bearing the responsibility for the technician’s work product, the profession has a responsibility to assure that technicians are properly educated and trained to undertake the work assigned to them. Without standardization of professional training requirements for technicians, the profession is deficient in meeting its responsibility to society. The 2002 white paper is mandatory reading for anyone concerned with this issue. It clearly lays out the challenge to the profession.


■■ A Closer Look at Pharmacy Technicians
An important component of discussions around the pharmacy workforce shortage issue is the appropriate use of technicians in various practice settings, the extent to which technicians are licensed and regulated, and the level of training necessary for technicians. Simultaneously, the growth of the number of pharmacy technicians presents a boon to the profession and a substantive challenge.
On one hand, the use of technicians helps to address the dramatic shortage of pharmacists that exists in today' s marketplace. 1 That shortage is expected to increase. Technicians are being used in a variety of ways in many different venues. As referenced in the "2002 White Paper on Pharmacy Technicians: Needed Changes Can No Longer Wait," it is noted that there are as many as 250,000 technicians operating in the United States. Functioning under the management of licensed pharmacists, technicians can perform repetitive, rote tasks that free pharmacists to deal with issues that necessitate their extensive training and expertise. In this manner, they provide a definite boon to the profession.
On the other hand, the lack of standardization in the preparation requirements for technicians is an Achilles' heel for the profession. While the profession vests technicians with the provision of direct service to the public, training and education requirements vary dramatically from state to state. In some jurisdictions, technicians must have successfully completed comprehensive education programs. Others mandate that technicians become certified through the Pharmacy Technician Certification Board. Employers often mandate in-service training to introduce the new technician to their roles, but this is at the discretion of the employer, creating great variations. Alarmingly, in some states, all that is required is a modest registration fee, without attestation to training of any sort.
The 2002 white paper is an update of a white paper on pharmacy technicians that was originally published by the American Pharmaceutical Association and the American Society of Health-System Pharmacists in 1996. The Council on Credentialing in Pharmacy authorized an update to the piece to reflect the dynamic changes that have occurred in the intervening years.
The Council on Credentialing in Pharmacy is dedicated to credentialing programs in pharmacy that meet established standards of quality that will contribute to significant improvement in the pharmaceutical care of patients and the overall public health. The council strives to introduce standardization into postlicensure training for pharmacists and training for technicians.

• American Society of Health-System Pharmacists • Commission for Certification in Geriatric Pharmacy
Similar to the individual pharmacist-supervisor bearing the responsibility for the technician' s work product, the profession has a responsibility to assure that technicians are properly educated and trained to undertake the work assigned to them. Without standardization of professional training requirements for technicians, the profession is deficient in meeting its responsibility to society. The 2002 white paper is mandatory reading for anyone concerned with this issue. It clearly lays out the challenge to the profession.

■■ Impact of the ALLHAT Study Results on Managed Care
The results of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) were released on December 17, 2002. Up to that time, many clinicians and managed care Pharmacy & Therapeutics (P&T) committees relied on the JNC VI (Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure) guidelines that were published in 1997. 1 Based on evidence-based studies, these guidelines strongly encouraged the use of low-cost diuretics and beta adrenergic blockers as the preferred initial therapy for most patients diagnosed with hypertension.
Though hundreds of clinical studies have been published since 1997, most had fewer patient numbers, lower-risk patients with milder forms of hypertension, and limited comparisons with other classes of pharmacological agents. The JNC has patiently waited for the results of ALLHAT before updating their national guidelines. How will the angiotensin converting enzyme inhibitors (ACEIs) and calcium channel blockers (CCBs) compare to the diuretics in patient outcomes? Are the increased costs of these agents balanced by improved clinical outcomes, including lower mortality and fewer hospitalizations? Many health care dollars have awaited the decision from ALLHAT and JNC VII on which drug is preferred for hypertension.
The ALLHAT study was a practice-based, randomized clinical trial of antihypertensive pharmacologic treatment (also cholesterol treatment in a subset) in more than 40,000 high-risk patients over the age of 55 years, with a large minority representation. To be included, patients had to have stage 1 or stage 2 hypertension with at least one additional cardiovascular risk factor: history of myocardial infarction (MI) or stroke, any revascularization procedure, documented atherosclerotic heart disease, type 2 diabetes mellitus, high-density lipoprotein (HDL) < 35 mg/dL, left ventricular hypertrophy (LVH), or cigarette smoking. Notable exclusions included patients with recent MI, stroke, congestive heart failure or angina, those with ejection fractions less than 35%, and those with renal insufficiency.
The primary objective of the ALLHAT study was to determine whether the combined incidence of fatal coronary heart disease (CHD) and nonfatal MI differs between a diuretic (chlorthalidone) versus an angiotensin converting enzyme inhibitor (lisinopril), a calcium channel blocker (amlodipine), or an alpha adrenergic blocker (doxazosin). These agents were selected as representative of their therapeutic class. Open-label drugs (atenolol, clonidine, reserpine, hydralazine) were allowed in combination therapy in order to reach the therapeutic goal of blood pressure <140/90 mm Hg. Secondary objectives included all-cause mortality, stroke, combined CHD, combined cardiovascular disease (CVD), and others.
The objective of the lipid-lowering arm was to determine if an HMG-CoA reductase agent (pravastatin) would decrease the risk of all-cause mortality in patients with and without CHD over the age of 55 years with moderate cholesterol elevations (and hypertension) compared to "usual care" (lifestyle change). For entry into this arm of the study, patients with documented CHD had to have a baseline fasting low-density lipoprotein (LDL) in the range of 100 mg/dL to 129 mg/dL, be without coronary heart disease, and have a baseline fasting LDL in the range of 120 mg/dL to 189 mg/dL. Patients were excluded if they were prescribed a cholesterol-lowering drug.
The scope of the ALLHAT trial is unprecedented in clinical research. The study started in 1994 and included 623 clinical sites that enrolled 42,418 patients in the hypertension arm and 10,355 patients in the cholesterol arm, with an average follow-up of 5 years. More than 500,000 visits were conducted, with more than 2 million bottles of prescription medication dispensed. Subset analysis included age, gender, ethnicity, and diabetes. The study was sufficiently powered to detect very small differences in clinical outcomes.
In January 2000, the doxazosin arm of the ALLHAT study was prematurely discontinued. When compared to chlorthalidone, patients assigned to doxazosin had no difference in the risk of fatal CHD, nonfatal MI, or total mortality. 2 However, the doxazosin arm did have a higher risk of stroke and combined CVD. In particular, the CHF risk was doubled (the 4-year rates were 8.13% versus 4.45%; relative risk was 2.04; 95% confidence interval 1.79-2.32; P<.001).
The initial results of the hypertension and cholesterol arms of the ALLHAT study have now been published. [3][4] In the cholesterol arm, the baseline characteristics for the statin and usual-care group were comparable. At year 4, the statins had a greater decrease in total cholesterol (17% versus 8%) and LDL (28% versus 11%) compared to the usual-care group. The average decrease in total cholesterol for all patients (statins and usual care) in this arm of the study was 9.6% compared to 20.2% in the 8 other major lipid trials. There were no statistical differences in all-cause mortality, CHD, or incidence of cancer between the groups. At year 4, 17% of the usual-care patients were placed on a statin, which may have impacted the final results. It is also possible that improved blood pressure control may have favorably impacted the clinical outcomes. The conclusion was that both lifestyle changes and statin therapy can lower cholesterol; these results are in agreement with the current National Cholesterol Education Program' s Adult Treatment Panel III guidelines. 5 The baseline characteristics of all 3 treatment groups in the hypertension arm of the study were comparable. At 5-year follow-up, the average blood pressure in the diuretic (chlorthalidone) group was 133.9/75.4 mm Hg versus amlodipine 134.7/74.6 mm Hg versus lisinopril 135.9/75.4 mm Hg. The difference in the systolic blood pressure between chlorthalidone and lisinopril was statistically significant (P<.001) as was the difference in diastolic blood pressure between chlorthalidone and amlodipine (P<.001); the differences may not be clinically significant, however. Nearly 60% of all treatment groups required additional therapy to reach the blood pressure goal; the impact of openlabel drugs on the results is unknown at this time. In the diuretic group, 68.2% of the patients were at their blood pressure goal at year 5 of the study compared to 61.2% on lisinopril (P<.001) and 66.3% on amlodipine (P=.09). Chlorthalidone and amlodipine were better tolerated than the lisinopril. In the diuretic group, there was a slight, but statistically significant, difference in biochemical abnormalities such as total cholesterol, potassium, and incidence of new diabetes.
There were no differences in the primary outcome (fatal CHD and/or nonfatal MI) among the treatment groups. However, there was an increase in the risk of stroke in the African American patient subset in the lisinopril group compared to the diuretic group (relative risk 1.40; 95% confidence interval 1.17-1.68; P value not stated in subset analysis). There was no increase in risk of stroke in the non-African American patient subset. The diuretic group had a significantly lower incidence of heart failure compared to amlodipine (relative risk 1.38, 95% confidence interval 1.25-1.52; P<.001) and lisinopril (relative risk 1.19, 95% confidence interval 1.07-1.31; P<.001). The higher incidence of biochemical abnormalities in the diuretic group did not adversely impact any clinical outcome.
One of the practical effects of these new ALLHAT study findings is that managed care pharmacists have additional support to recommend diuretics as first-line agents for hypertension. In the past, most of us have encouraged the use of diuretics based on the results of older studies and their lower cost. Their use has been validated with additional evidence from the ALLHAT study findings that demonstrated equal or superior clinical outcomes with the diuretics compared to the highly marketed, widely prescribed, and more expensive ACEIs and CCBs. The ALLHAT study results will no doubt be challenged vigorously by the pharmaceutical industry, and further analyses of the data will be forthcoming over the next one to two years.
There is certainly a place for ACEIs, CCBs, and beta adrenergic blockers in the management of hypertension, especially in